The precese relationship between aging of articular cartilage and osteoarthritis (OA) of the major synovial joints remains unknown. Alterations in the structure and composition of human articular cartilage proteoglycans as a function of decade-life suggest differences if compared to cartilage proteoglycans derived from age-matched individuals with debilitating OA. Can cartilage derived from aged nonpathological specimens ever develop the proteoglyan "phenotype" of OA or are the processes separate pathogenetic entities? A delineation of the relationship between aging and OA in man remains difficult because of the relative inability to study changes in articular cartilage proteoglycans from the same individual over a time course consonant with the aging process and during the time period of 20-30 years in which cellular and surface changes occur in articular cartilage resulting in OA lesions. Typically, the latter include a degeneration of the articular cartilage, abnormal cartilage and bone formation (osteochondrophytic spurs) and cystic changes in subchondral bone. Joint remodeling occurs during aging and in OA of the hip. Established organ-explant and cell culture techniques have been used in this laboratory to explore the in vitro behavior of young, aged and OA human hip, knee and ankle cartilage. Our findings suggest that the OA is characterized by an elevated activity of neutral pH active enzymes that alter the structure of the neosynthetic and endogenous proteoglycans. This results in a defective extracellular matrix with altered physiochemical functions. The nature of these enzyme activities and their effect on proteoglycan in the young and aged cartilage is not known. The principal objective of this proposal is to address the hypothesis that human cartilage maintained in organ culture for lengthy period of time undergoes alterations in the structure of neosynthetic proteoglycans which is independent of the donor age of the cartilage initially explanted. We will delineate changes in proteoglycans in this in vitro "aging model" by classical biochemical techniques and by using monoclonal antibodies that react with specific epitopes on proteoglycan. Chondrocytes derived from young, aged nonpathological, and OA cartilage will be maintained in culture to compare changes in proteoglycans as a function of age in culture and subpassage, in order to better define proteoglycan metabolism at the cellular level. Further understanding of the relationship delineating changes in proteoglycans during aging in vitro should shed light on the possible contribution of the aging process to OA.